The long-term goal of this project is to identify the genes that are required to build a nervous system. The nervous system is composed of two general classes of cells: neurons, which transmit information in the form of electrical impulses, and glial cells, which facilitate impulse transmission and survival of neurons. How neurons and glial cells are formed and organized into functional neural circuits during development is still poorly understood. The project design draws from the well-validated idea that mutations that disrupt neural development reveal critical genes. Building on the expertise of the collaborating team of investigators, this work will discover genes that are necessary for development of motor axons and glial cells that wrap central and peripheral nerves. The project will use zebrafish as a model system, which permits the careful observations necessary to find rare mutations that cause specific neural defects. The first aim of the project is to screen families of mutagenized zebrafish embryos for defects of motor axons and two distinct populations of central and peripheral myelinating glial cells by examining expression of transgenically encoded fluorescent reporter proteins that reveal cell morphologies. The second aim is to determine how each mutation causes its corresponding defect through careful characterization of cellular defects, using immunohistochemical and transgenic cell marking techniques and in vivo time-lapse imaging. The third aim is to determine the chromosomal location of each mutation and identify the affected genes. Completion of this project will enhance understanding of the genetic bases of neurological disorders involving the sensory system or glia and provide genes that might be used to promote neural repair following injury or disease. PUBLIC HEALTH RELEVANCE: This project will identify genes that are necessary to build a nervous system. It will provide a better understanding of how the nervous system develops and potentially lead to new strategies to promote neural repair following disease or injury.